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Association of Shp2 with phosphorylated IL-22R1 is required for interleukin-22-induced MAP kinase activation Free
Songshu Meng1,+, Qiu Gui1,+, Qing Xu2, Kaixin Lu1, Xinan Jiao1, Jian Fan1, Baoxue Ge3, Yuehai Ke4, Shengping Zhang5, Jie Wu6,*, and Chuangui Wang5,*
1College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009, China
2Tenth People's Hospital, Tongji University, Shanghai 200072, China
3Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, China
4School of Medicine, Zhejiang University, Hangzhou 310058, China
5Institute of Biomedical Sciences, School of Life Science, East China Normal University, Shanghai 200062, China
6Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, and Department of Oncologic Sciences, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA *Correspondence to:Jie Wu, Tel: +1-813-745-6713; E-mail: Jerry.Wu@moffitt.org; Chuangui Wang, Tel: +86-21-54345019; E-mail: cgwang@bio.ecnu.edu.cn
J Mol Cell Biol, Volume 2, Issue 4, August 2010, 223-230,  https://doi.org/10.1093/jmcb/mjq017
Keyword: interleukin-22, IL-22 receptor 1 (IL-22R1), Shp2, MAP kinase, STAT3
Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines produced by activated T cells and is involved in several tissue responses. IL-22 signals through a heterodimeric receptor composed of IL-22 receptor 1 (IL-22R1) and IL-10R2, and the intracellular signaling pathways mediated by IL-22 receptor are not completely known. Here we investigate the effect of Src homology-2 containing protein-tyrosine phosphatase (Shp2) on IL-22 signaling pathway using SW480 colon cancer cells as a model. The results show that IL-22 induces IL-22R1 phosphorylation, and Shp2 is recruited to the tyrosine phosphorylated IL-22R1 upon IL-22 stimulation. Furthermore, Tyr251 and Tyr301 of IL-22R1 are required for Shp2 binding to the IL-22R1. Shp2 binding to IL-22R1 and Shp2 protein tyrosine phosphatase activity are required for activation of MAP kinases and signal transducer and activator of transcription (STAT3) phosphorylation by IL-22. These results reveal a critical role of Shp2 in IL-22 mediated signal transduction pathways.

Volume 2, Issue 4
August 2010